Centro de Neurobiología y Plasticidad del Desarrollo, Departamento de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Gran Bretaña 1111, Playa Ancha, Valparaíso, Chile.
Neurobiol Dis. 2010 Jan;37(1):208-17. doi: 10.1016/j.nbd.2009.10.004. Epub 2009 Oct 12.
Beta-amyloid (Abeta) deposition is one important pathological hallmark in Alzheimer's disease (AD). However, low levels of Abeta may modify critical endogenous protection systems before neurodegeneration occurs. We examined the time-course effect of sublethal concentrations of Abeta on total BDNF (panBDNF), BDNF transcripts (I, II, IV and VI), trkB.FL, trkB.T1 and p75(NGFR) mRNA expression in cultured cortical neurons. We have shown that Abeta exhibited a dual response on BDNF mRNA, i.e. an increase at short times (3-5 h) and a dramatic decrease at longer times (24 or 48 h). The early increase in BDNF expression seems to be driven by increased expression of transcripts I and IV. The BDNF drop was specific since did not occur for other mRNAs examined. The BDNF protein content showed a similar profile but did not follow the dramatic reduction as its encoding mRNA. These observations may help to explain cognitive deficits observed at initial stages of AD.
β-淀粉样蛋白（Abeta）沉积是阿尔茨海默病（AD）的一个重要病理标志。然而，在神经退行性变发生之前，Abeta 的低水平可能会修饰关键的内源性保护系统。我们研究了亚致死浓度 Abeta 对培养皮质神经元中总 BDNF（panBDNF）、BDNF 转录本（I、II、IV 和 VI）、trkB.FL、trkB.T1 和 p75（NGFR）mRNA 表达的时间进程效应。我们已经表明，Abeta 在 BDNF mRNA 上表现出双重反应，即在短时间（3-5 小时）内增加，而在较长时间（24 或 48 小时）内急剧减少。BDNF 表达的早期增加似乎是由 I 和 IV 转录本表达增加驱动的。BDNF 的下降是特异性的，因为其他检查的 mRNA 没有发生这种情况。BDNF 蛋白含量表现出相似的模式，但没有像其编码 mRNA 那样急剧减少。这些观察结果可能有助于解释在 AD 的初始阶段观察到的认知缺陷。
